Specificity screening of CAR T cells

Chimeric antigen receptor (CAR) T cell therapy involves engineering the patient’s own immune cells to recognise and attack a specific tumour. It has shown long-term promise in patients with advanced disease. As the therapy works by harnessing the immune system it is crucial that there is no off-target activity that could promote an inappropriate immune response and be very dangerous for the patient.

Retrogenix’s standard approach for specificity screening of CAR T cells initially focused solely on the single chain variable fragment (scFv) that will ultimately be engineered onto the T cells. However, we have now also developed a methodology for labelling and screening the whole CAR T cells themselves. This can provide even greater confidence in the specificity of the therapy. It also provides further support for IND submissions.

Screen scFvs or whole CAR T cells

Retrogenix has two approaches for off-target screening of CAR T cells:

Screen the antigen recognition element – the scFv

Screen whole engineered CAR T cells

Early specificity screening helps select the right scFvs in order to maximise the chances of producing the most promising potential CAR T therapy. This can be followed later by screening of the whole engineered T cell to provide a more physiological assessment of off-target liability.

Download our poster describing the how the Retrogenix human cell microarray technology has been optimised to screen whole CAR T cells for specific interactions, helping reduce the risk of unanticipated off-target adverse effects in the development of novel immunotherapies.

FAQ: “How long does a screen take?”

Projects typically take around 8 weeks from when we receive materials through to delivering the results and data package. A single molecule screen using a routine detection system can take as little as 6 weeks. Longer lead times (for example 12 weeks) may be required for some studies including projects where a new detection method is being used as this will need to be optimised with the Retrogenix technology.

We are delighted with the work that Retrogenix has done for us. Their technology has been extremely useful in identifying and confirming the cell surface interaction partners for our antibodies and other protein ligands. The work is always carried out to a high quality standard and turned around in good time.